全部 标题 作者
关键词 摘要


New 1,2,3-Triazole Iminosugars Derivatives Using Click Chemistry

DOI: 10.1155/2012/394574

Full-Text   Cite this paper   Add to My Lib

Abstract:

The click concept refers ease, efficient, and the selective chemicals transformations. In this study, a novel regiospecific copper (I)-catalyzed 1, 3-dipolar of terminal alkynes to azide provided a practicable synthetic pathway of triazole iminosugars derivatives. A series of new triazole-pyrrolidinols are reported in good yield. 1. Introduction There are considerable interests in the design of molecules that are able to mimic carbohydrates which play critical roles in various biological events. This is shown by the following example, the 1-deoxynojirimycin (DNJ) family, for which DNJ itself is a competitive inhibitor of α-D-glucosidase ( 25?μM) [1], while its derivatives Miglustat (N-nBu DNJ, Zavesa) and Miglitol (N-hydroxyethyl DNJ, Glyset, or Diastabol) have already found therapeutic applications in Gaucher’s disease [2] and type 2 (noninsulin-dependant mellitus) diabetes, respectively [3, 4] (Figure 1). Recently, researches have increasingly accorded to new iminosugars from click chemistry [5]. Figure 1: Structure of inhibitors of glycosidases. The term click chemistry was introduced by Sharpless and coworkers and promotes the use of efficient, selective, and versatile chemical reactions in synthetic chemistry [6]. The basic reaction, which is nowadays summed up under the name “Sharpless-type click reaction,” is a variant of the Huisgen 1,3-dipolar cycloaddition reaction between C–C triple bonds and alkyl azides [7, 8] (Scheme 1). Scheme 1: 1,3-dipolar cycloaddition reaction. Meldal and coworkers published a paper in 2002 that describes the acceleration of this process by CuI salts that leads to a reaction at 25°C in quantitative yields. It was mentioned that the organic azides and the terminal alkynes are united to afford 1,4-regioisomers of 1,2,3-trialoes as sole products [9]. The source of Cu(I) salts commonly used involves the reduction of copper(II) sulfate by sodium ascorbate [9], although other conditions have been described, such as Cu(I) [10] salts, Cu(I) complexes [11] and stabilized derivatives of Cu(I) [9]. The bases used are mostly triethylamine, 2,6-lutidine and N,N-diisopropylethylamine (DIPEA). 1.1. Click Chemistry and Synthesis of Iminosugars Derivatives The application of CuAAC-catalysed reactions for the synthesis of new α-glucosidase inhibitors containing a 1-deoxynojirimycin (DNJ) was described by Murphy and coworkers. These compounds indicate that it is possible to modulate the potency and the selectivity towards different glycosidases [5] (Figure 2). Figure 2: Structures of triazole iminosugars as potential glycosidase

References

[1]  A. Mitrakou, N. Tountas, A. E. Raptis, R. J. Bauer, H. Schulz, and S. A. Raptis, “Long-term effectiveness of a new alpha-glucosidase inhibitor (BAY m1099-miglitol) in insulin-treated type 2 diabetes mellitus,” Diabetic Medicine, vol. 15, no. 8, pp. 657–660, 1998.
[2]  L. J. Scott and C. M. Spencer, “Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus,” Drugs, vol. 59, no. 3, pp. 521–549, 2000.
[3]  T. M. Block, X. Lu, F. M. Platt et al., “Secretion of human hepatitis B virus is inhibited by the imino sugar N-butyldeoxynojirimycin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 6, pp. 2235–2239, 1994.
[4]  A. Mehta, S. Carrouee, B. Conyers, et al., “Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications,” Hepatology, vol. 33, no. 6, pp. 1488–1495, 2001.
[5]  B. Andersen, A. Rassov, N. Westergaard, and K. Lundgren, “Inhibition of glycogenolysis in primary rat hepatocytes by 1,4-dideoxy-1,4-imino-D-arabinitol,” Biochemical Journal, vol. 342, no. 3, pp. 545–550, 1999.
[6]  Y. Zhou, Y. Zhao, K. M. O'Boyle, and P. V. Murphy, “Hybrid angiogenesis inhibitors: synthesis and biological evaluation of bifunctional compounds based on 1-deoxynojirimycin and aryl-1,2,3-triazoles,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 3, pp. 954–958, 2008.
[7]  H. C. Kolb, M. G. Finn, and K. B. Sharpless, “Click chemistry: diverse chemical function from a few good reactions,” Angewandte Chemie International Edition, vol. 40, no. 11, pp. 2004–2021, 2001.
[8]  R. Huisgen, G. Szeimies, and L. Mobius, “1.3-Dipolare Cycloadditionen, XXXII. Kinetik der Additionen organischer Azide an CC-Mehrfachbindungen,” Chemische Berichte, vol. 100, no. 8, pp. 2494–2507, 1967.
[9]  C. W. Tornoe, C. Christensen, and M. Meldal, “Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides,” The Journal of Organic Chemistry, vol. 67, no. 9, pp. 3057–3064, 2002.
[10]  K. V. Gothelf and K. A. Joergensen, “Asymmetric 1,3-dipolar cycloaddition reactions,” Chemical Reviews, vol. 98, no. 2, pp. 863–910, 1998.
[11]  T. R. Chan, R. Hilgraf, K. B. Sharpless, and V. V. Fokin, “Polytriazoles as copper(I)-stabilizing ligands in catalysis,” Organic Letters, vol. 6, no. 17, pp. 2853–2855, 2004.
[12]  J. Diot, M. I. Garcoa-Moreno, S. G. Gouin, C. O. Mellet, and K. Kovensky, “Multivalent iminosugars to modulate affinity and selectivity for glycosidases,” Organic and Biomolecular Chemistry, vol. 7, no. 2, pp. 357–363, 2009.
[13]  I. Kumar, N. A. Mir, C. V. Rode, and B. P. Wakhloo, “Intramolecular Huisgen [3+2] cycloaddition in water: synthesis of fused pyrrolidine-triazoles,” Tetrahedron, vol. 23, no. 3-4, pp. 225–229, 2012.
[14]  V. Haridas, K. Lal, Y. K. Sharma, and S. Upreti, “Design, synthesis, and self-assembling properties of novel triazolophanes,” Organic Letters, vol. 10, no. 8, pp. 1645–1647, 2008.
[15]  C. Benhaoua, “One-pot synthesis of pyrrolidine-2-ones from erythruronolactone and amine,” Organic Chemistry International, vol. 2012, Article ID 482952, 6 pages, 2012.
[16]  A. Maisonial, P. Serafin, M. Tra?kia et al., “Click chelators for platinum-based anticancer drugs,” European Journal of Inorganic Chemistry, vol. 2008, no. 2, pp. 298–305, 2008.

Full-Text

comments powered by Disqus